Meta-analysis of the effect of CYP2B6, CYP2A6, UGT2B7 and CAR polymorphisms on efavirenz plasma concentrations

2019 ◽  
Vol 74 (11) ◽  
pp. 3281-3290 ◽  
Author(s):  
Pedro Ayuso ◽  
Megan Neary ◽  
Justin Chiong ◽  
Andrew Owen
Keyword(s):  
Ethnic Differences ◽  
Effect Size ◽  
Meta Analysis ◽  
Constitutive Androstane Receptor ◽  
Plasma Concentrations ◽  
Pharmacokinetic Parameters ◽  
Primary Metabolism ◽  
Standard Mean Difference ◽  
The Impact ◽  
Review Manager

Abstract Background Efavirenz primary metabolism is catalysed by CYP2B6 with minor involvement of CYP2A6. Subsequently, phase I metabolites are conjugated by UGT2B7, and constitutive androstane receptor (CAR) has been shown to transcriptionally regulate many relevant enzymes and transporters. Several polymorphisms occurring in the genes coding for these proteins have been shown to impact efavirenz pharmacokinetics in some but not all studies. Objectives A meta-analysis was performed to assess the overall effect of CYP2B6 rs3745274, CYP2A6 (rs28399454, rs8192726 and rs28399433), UGT2B7 (rs28365062 and rs7439366) and NR1I3 (rs2307424 and rs3003596) polymorphisms on mid-dose efavirenz plasma concentrations. Methods Following a literature review, pharmacokinetic parameters were compiled and a meta-analysis for these variants was performed using Review Manager and OpenMetaAnalyst. A total of 28 studies were included. Results Unsurprisingly, the analysis confirmed that individuals homozygous for the T allele for CYP2B6 rs3745274 had significantly higher efavirenz concentrations than those homozygous for the G allele [weighted standard mean difference (WSMD) = 2.98; 95% CI 2.19–3.76; P < 0.00001]. A subgroup analysis confirmed ethnic differences in frequency but with a similar effect size in each ethnic group (P = 0.96). Associations with CYP2A6 and UGT2B7 variants were not statistically significant, but T homozygosity for CAR rs2307424 was associated with significantly lower efavirenz concentrations than in C homozygotes (WSMD = −0.32; 95% CI −0.59 to −0.06; P = 0.02). Conclusions This meta-analysis provides the overall effect size for the impact of CYP2B6 rs3745274 and NR1I3 rs2307424 on efavirenz pharmacokinetics. The analysis also indicates that some previous associations were not significant when interrogated across studies.

Evaluating the effectiveness of interventions to reducing screen time in children: meta-analysis of randomized controlled trials

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Duygu Akçay ◽  
Nuray Barış
Keyword(s):  
Effect Size ◽  
Subgroup Analysis ◽  
Screen Time ◽  
Meta Analysis ◽  
Intervention Group ◽  
Evidence Base ◽  
Control Group ◽  
Content Type ◽  
Mean Differences ◽  
The Impact

Purpose The purpose of this paper is to evaluate the impact of interventions focused on reducing screen time in children. Design/methodology/approach Studies that aim to investigate the effects of interventions aimed at reducing the time spent in front of the screen (i.e. screen time). A Random-effects model was used to calculate the pooled standard mean differences. The outcome was to evaluate the screen time in children in the 0–18 age range. A subgroup analysis was performed to reveal the extent to which the overall effect size varied by subgroups (participant age, duration of intervention and follow). Findings For the outcome, the meta-analysis included 21 studies, and the standard difference in mean change in screen time in the intervention group compared with the control group was −0.16 (95% confidence interval [CI], −0.21 to −0.12) (p < 0.001). The effect size was found to be higher in long-term (=7 months) interventions and follow-ups (p < 0.05). Originality/value Subgroup analysis showed that a significant effect of screen time reduction was observed in studies in which the duration of intervention and follow-up was =7 months. As the evidence base grows, future researchers can contribute to these findings by conducting a more comprehensive analysis of effect modifiers and optimizing interventions to reduce screen time.

scholarly journals Effects of exercise training on physical and psychosocial health in children with chronic respiratory disease: a systematic review and meta-analysis

2018 ◽  
Vol 4 (1) ◽  
pp. e000409 ◽  
Author(s):  
Barbara Joschtel ◽  
Sjaan R Gomersall ◽  
Sean Tweedy ◽  
Helen Petsky ◽  
Anne B Chang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Lung Function ◽  
Exercise Training ◽  
Respiratory Disease ◽  
Effect Size ◽  
Meta Analysis ◽  
Chronic Respiratory Disease ◽  
Cardiovascular Fitness ◽  
Standard Mean Difference ◽  
Children With Asthma

IntroductionChronic disease in children is increasing, including the prevalence of chronic respiratory diseases such as asthma, cystic fibrosis (CF), bronchiectasis and bronchopulmonary dysplasia (BPD). The aim of this systematic review and meta-analysis was to evaluate the effects of exercise training on health outcomes in children with chronic respiratory disease.MethodFive databases were searched for randomised controlled trials investigating the effects of exercise training on children with chronic respiratory disease. Following the PRISMA guidelines, eligible studies were identified and data were extracted. A meta-analysis was conducted for the outcomes cardiovascular fitness, lung function and quality of life (QoL).ResultsThe initial search returned 3688 papers. Twenty-seven (17 in children with asthma, 10 in children with CF) were included in the systematic review and 24 of these were included in the meta-analysis. No studies were identified in children with bronchiectasis or BPD. Included papers had a total of 1009 participants aged 8–20 years. In addition to cardiovascular fitness, lung function and QoL, studies also assessed pulmonary function, respiratory muscle strength, muscular strength and inflammation. Meta-analysis showed a large significant effect size in favour of exercise for cardiovascular fitness (peak VO2) (standard mean difference (SMD)=1.16, 95%  CI 0.61 to 1.70) and QoL (SMD=1.27, 95% CI 0.72 to 1.82) as well as a small, non-significant effect size for lung function (FEV1) (SMD=0.02, 95% CI -0.38 to 0.42).ConclusionExercise training significantly improves cardiovascular fitness and QoL in children with asthma and CF. Further research is needed, particularly in children with bronchiectasis and BPD.

scholarly journals Reliability of Computerized Neurocognitive Tests for Concussion Assessment: A Meta-Analysis

2017 ◽  
Vol 52 (9) ◽  
pp. 826-833 ◽  
Author(s):  
James L. Farnsworth ◽  
Lucas Dargo ◽  
Brian G. Ragan ◽  
Minsoo Kang
Keyword(s):  
Correlation Coefficient ◽  
Intraclass Correlation Coefficient ◽  
Effect Size ◽  
Sampling Error ◽  
Meta Analysis ◽  
Intraclass Correlation ◽  
Cognitive Testing ◽  
Test Duration ◽  
Neurocognitive Tests ◽  
The Impact

Objective:  Although widely used, computerized neurocognitive tests (CNTs) have been criticized because of low reliability and poor sensitivity. A systematic review was published summarizing the reliability of Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) scores; however, this was limited to a single CNT. Expansion of the previous review to include additional CNTs and a meta-analysis is needed. Therefore, our purpose was to analyze reliability data for CNTs using meta-analysis and examine moderating factors that may influence reliability. Data Sources:  A systematic literature search (key terms: reliability, computerized neurocognitive test, concussion) of electronic databases (MEDLINE, PubMed, Google Scholar, and SPORTDiscus) was conducted to identify relevant studies. Study Selection:  Studies were included if they met all of the following criteria: used a test-retest design, involved at least 1 CNT, provided sufficient statistical data to allow for effect-size calculation, and were published in English. Data Extraction:  Two independent reviewers investigated each article to assess inclusion criteria. Eighteen studies involving 2674 participants were retained. Intraclass correlation coefficients were extracted to calculate effect sizes and determine overall reliability. The Fisher Z transformation adjusted for sampling error associated with averaging correlations. Moderator analyses were conducted to evaluate the effects of the length of the test-retest interval, intraclass correlation coefficient model selection, participant demographics, and study design on reliability. Heterogeneity was evaluated using the Cochran Q statistic. Data Synthesis:  The proportion of acceptable outcomes was greatest for the Axon Sports CogState Test (75%) and lowest for the ImPACT (25%). Moderator analyses indicated that the type of intraclass correlation coefficient model used significantly influenced effect-size estimates, accounting for 17% of the variation in reliability. Conclusions:  The Axon Sports CogState Test, which has a higher proportion of acceptable outcomes and shorter test duration relative to other CNTs, may be a reliable option; however, future studies are needed to compare the diagnostic accuracy of these instruments.

scholarly journals Efectos de la intervención en conciencia morfológica sobre la lectura, escritura y comprensión: Meta-análisis

2015 ◽  
Vol 32 (1) ◽  
pp. 60 ◽  
Author(s):  
Mercedes I. Rueda-Sánchez ◽  
Patricia López-Bastida
Keyword(s):  
Effect Size ◽  
Selection Criteria ◽  
Meta Analysis ◽  
Reading Difficulties ◽  
Morphological Awareness ◽  
Awareness Training ◽  
Moderating Variables ◽  
Reading Vocabulary ◽  
Morphological Awareness Training ◽  
The Impact

The aim is to check, through a meta-analysis, the impact of morphological awareness training on writing, reading, comprehension and vocabulary of grade schooler. 31 studies were included in the meta-analysis; they were obtained from 19 articles that meet the selection criteria. Morphological awareness instruction has a high-medium and significant effect size in studied variables of literacy. On writing, <em>g</em>=0.491, <em>SE</em>=0.078, <em>IQ</em>=0339-0643, <em>p</em>=.000, reading, <em>g</em>=0.473, <em>SE</em>=0.096, <em>IQ</em>=0284-0662, <em>p</em>=.000, comprehension, <em>g</em>=0.468, <em>SE</em>=0.123, <em>IQ</em>=0227-0708, <em>p</em>= .000 and finally vocabulary, <em>g</em>=0.501, <em>SE</em>=0.152, <em>IQ</em>=0203-0798, <em>p</em>= .001. The test of Heterogeneity <em>Q</em> is only significant on writing so other moderating variables were explored but no differences between groups were found. It shows morphological awareness training improves reading, vocabulary and comprehension of grade schooler with and without reading difficulties. Nevertheless, the results on writing are more heterogeneous.

Abstract WMP37: Methodological Quality and Meta-Analysis of Animal Studies of Mesenchymal Stromal Cells for Ischemic Stroke

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Kate Xie* ◽  
Quynh Vu* ◽  
Mark Eckert ◽  
Weian Zhao ◽  
Steven C Cramer
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Effect Size ◽  
Stromal Cells ◽  
Methodological Quality ◽  
Meta Analysis ◽  
Quality Score ◽  
Behavioral Effects ◽  
Behavioral Measure ◽  
Routes Of Administration ◽  
The Impact

INTRODUCTION: Mesenchymal stromal cells (MSC) are multipotent cells that support numerous restorative processes after stroke. The ease of isolation and immunoprivileged status of MSC have stimulated numerous preclinical stroke studies. We performed a meta-analysis to estimate study quality, size of behavioral effects, and the impact of variables such as timing of MSC administration in relation to stroke onset. METHODS: Studies of MSC and stroke were identified through PubMed and Web of Science. Studies of hemorrhage, not in English, or using modified MSC were excluded. A Quality Score was determined for each study, estimating methodological quality using 10 criteria derived from STAIR guidelines, with higher Quality Scores reflecting greater compliance with issues such as randomization and outcome blinding. Outcome data extracted for MSC and control arms were used to derive estimates of effect size using Cohen’s d. RESULTS: A total of 46 studies met criteria, with 39 studying rats, 6 mice, and 1 primates. There were 61 treatment groups, as some studies had >1 independent MSC treatment arms; MSC were introduced intravenously in 41, intracerebrally in 15, and intraarterially in 6. MSC source was rat in 24, human in 16, and mouse in 6. Time of MSC administration ranged from 5 weeks pre- to 1 month post-stroke. MSC dose ranged from 1x10^4 to 3.25x10^7. The median Quality Score was 6 (IQR 5-7). Quality Score was not related to time of MSC administration relative to stroke or to behavioral effect size. Median effect size was 2.05 for the Modified Neurological Severity Scale (n=23), 1.88 for Adhesive Removal Test (n=19), and 2.70 for the Rotarod Test (n=14). Effect sizes were substantial across all routes of administration and differed only for the mNSS (p<0.04), favoring the IC route. Effect size did not vary with time of MSC administration relative to stroke for any behavioral measure. CONCLUSIONS: The quality of preclinical MSC stroke studies has generally been good. MSC consistently provide very large behavioral benefits, across scales and routes of administration. The magnitude of behavioral effects was not related to the Quality Score or to the time of MSC administration relative to stroke. These findings support translation of MSC to human trials.

scholarly journals The Impact of Javanica Oil Emulsion Injection on Chemotherapy Efficacy and Cellular Immune Indicators in Patients with Advanced NSCLC: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-12
Author(s):  
Huilin Xu ◽  
Zhucheng Yin ◽  
Anbing He ◽  
Dedong Cao
Keyword(s):  
Advanced Nsclc ◽  
Karnofsky Performance Status ◽  
Meta Analysis ◽  
Objective Response ◽  
Cochrane Library ◽  
Combination Group ◽  
Control Group ◽  
Oil Emulsion ◽  
Standard Mean Difference ◽  
The Impact

Background. This meta-analysis aimed to evaluate the efficacy and safety of Javanica oil emulsion injection (JOI) combined with chemotherapy versus chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). Methods. Electronic databases including EMBASE, PUBMED, the Cochrane library, and Chinese Biological Medical disc (CBM) were searched until May 2018. The clinical trials reporting efficacy and immune function of JOI combined with chemotherapy versus chemotherapy in advanced NSCLC were included according to the inclusion and exclusion criteria. Stata 11 and RevMan 5.3 were used for meta-analysis. Results. Twenty-four studies involving 2089 cases were included. The results of the meta-analysis showed that there were significant differences in objective response rate (risk ratio (RR) = 1.17; 95% confidence interval (CI): 1.05–1.29; P<0.05), improvement in Karnofsky Performance Status (standard mean difference (SMD) = 1.59; 95% CI: 1.41–1.77; P<0.01), incidence of adverse events (RR = 0.78; 95% CI: 0.7–0.87; P<0.05), percentage changes of CD3+ cells (SMD = 2.0; 95% CI: 1.49–2.50; P<0.01), CD4+ cells (SMD = 1.55; 95% CI, 1.2–1.9; P<0.01), natural killer cells (SMD = 1.98; 95% CI: 1.15–2.82; P<0.01), but not CD8+ (SMD = −1.44; 95% CI: −4.53–1.65; P=0.36), and value of CD4+/CD8+ (SMD = 0.32; 95% CI: 0.28–0.36; P<0.01) between the JOI combination group and control group. Funnel plot and Begg’s and Egger’s analysis indicated that there was no significant publication bias (P>0.05). Conclusions. JOI may be effective to improve the efficacy of chemotherapy in advanced NSCLC patients, accompanied with better levels of immune cells.

scholarly journals Considering the methodological limitations in the evidence base of antidepressants for depression: a reanalysis of a network meta-analysis

BMJ Open ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. e024886 ◽  
Author(s):  
Klaus Munkholm ◽  
Asger Sand Paludan-Müller ◽  
Kim Boesen
Keyword(s):  
Systematic Review ◽  
Clinical Study ◽  
Effect Size ◽  
Meta Analysis ◽  
Evidence Base ◽  
Risk Of Bias ◽  
Depression Symptom ◽  
Meta Analyses ◽  
The Impact ◽  
Clinical Study Reports

ObjectivesTo investigate whether the conclusion of a recent systematic review and network meta-analysis (Ciprianiet al) that antidepressants are more efficacious than placebo for adult depression was supported by the evidence.DesignReanalysis of a systematic review, with meta-analyses.Data sources522 trials (116 477 participants) as reported in the systematic review by Ciprianiet aland clinical study reports for 19 of these trials.AnalysisWe used the Cochrane Handbook’s risk of bias tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to evaluate the risk of bias and the certainty of evidence, respectively. The impact of several study characteristics and publication status was estimated using pairwise subgroup meta-analyses.ResultsSeveral methodological limitations in the evidence base of antidepressants were either unrecognised or underestimated in the systematic review by Ciprianiet al. The effect size for antidepressants versus placebo on investigator-rated depression symptom scales was higher in trials with a ‘placebo run-in’ study design compared with trials without a placebo run-in design (p=0.05). The effect size of antidepressants was higher in published trials compared with unpublished trials (p<0.0001). The outcome data reported by Ciprianiet aldiffered from the clinical study reports in 12 (63%) of 19 trials. The certainty of the evidence for the placebo-controlled comparisons should be very low according to GRADE due to a high risk of bias, indirectness of the evidence and publication bias. The mean difference between antidepressants and placebo on the 17-item Hamilton depression rating scale (range 0–52 points) was 1.97 points (95% CI 1.74 to 2.21).ConclusionsThe evidence does not support definitive conclusions regarding the benefits of antidepressants for depression in adults. It is unclear whether antidepressants are more efficacious than placebo.

scholarly journals The Effect of Acute Hypohydration on Indicators of Glycemic Regulation, Appetite, Metabolism and Stress: A Systematic Review and Meta-Analysis

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2526
Author(s):  
Mitchell E. Zaplatosch ◽  
William M. Adams
Keyword(s):  
Peptide Yy ◽  
Meta Analysis ◽  
Body Water ◽  
Hormonal Changes ◽  
Water Losses ◽  
Standard Mean Difference ◽  
Total Body ◽  
And Performance ◽  
Glycemic Regulation ◽  
The Impact

Evidence synthesizing the effects of acute body water losses on various markers of glycemic regulation, appetite, metabolism, and stress is lacking. Thus, the purpose of this review was to summarize the response of various hormonal changes involved in these physiologic functions to dehydration. A comprehensive literature search for peer-reviewed research in the databases PubMed, Scopus, CINAHL, and SportDiscus was conducted. Studies were included if they contained samples of adults (>18 years) and experimentally induced dehydration as measured by acute body mass loss. Twenty-one articles were eligible for inclusion. Findings suggested cortisol is significantly elevated with hypohydration (standard mean difference [SMD] = 1.12, 95% CI [0.583, 1.67], p < 0.0001). Testosterone was significantly lower in studies where hypohydration was accompanied by caloric restriction (SMD= −1.04, 95% CI [−1.93, −0.14], p = 0.02), however, there were no changes in testosterone in studies examining hypohydration alone (SMD = −0.17, 95% CI [−0.51 0.16], p = 0.30). Insulin and ghrelin were unaffected by acute total body water losses. Acute hypohydration increases markers of catabolism but has a negligible effect on markers of glycemic regulation, appetite, anabolism and stress. Given the brevity of existing research, further research is needed to determine the impact of hydration on glucagon, leptin, peptide YY and the subsequent outcomes relevant to both health and performance.

scholarly journals Clinical determinants associated with quality of life for people who live with HIV/AIDS: a Meta-analysis

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Hesam Ghiasvand ◽  
Katherine M. Waye ◽  
Mehdi Noroozi ◽  
Gholamreza Ghaedamini Harouni ◽  
Bahram Armoon ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Confidence Interval ◽  
Effect Size ◽  
Meta Analysis ◽  
Random Effect Model ◽  
Cd4 Count ◽  
Co Morbidity ◽  
The Impact ◽  
Hiv Aids

Abstract Background During recent years, Quality of Life (QoL) is a significant assessment factor in clinical trials and epidemiological researches due to the advent of Antiretroviral Therapy (ART), Human Immunodeficiency Virus (HIV) has become a manageable,chronic disease. With regards, more attention must be paid to the QoL of infected patients. Limited evidence exists on the impact of ART on QoL among HIV infected patients. Due to lacking of a systematic approach to summarizing the available evidence on the clinical determinants of People Who Live with HIV/AIDS (PWLHs’) QoL, this study aimed to analyze the impact of clinical determinants (ART experience, CD4 count < 200, co-morbidities, time diagnosis and accessibility to cares) on QoL among PWLHs’. Methods This study was designed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). PubMed, Science Direct, Web of Science, and Cochrane electronic databases were searched in February 2017 to identify all past studies that discussed social and behavioral characteristics of QoL in PLWHA. To recognize effective factors on social and behavioral QoL, a meta-analysis was conducted. Polled Odds Ratios (ORs) were utilized at a 95% confidence level. Since sampling methods differed between articles in the systematic review, we evaluated pooled estimates using a random effect model. Metan, metareg, metacum, and metabias commands in STATA version 13.0 were applied to analyze the data. Results Our findings indicated that ART has a positive impact on QoL, with a pooled effect size at approximately 1.04 with a confidence interval between 0.42 to 1.66 which indicates this impact is not very considerable and may be relatively neutral. The pooled effect size for CD4 count on QoL was .29 (95%CI = .22–.35), indicating that there is a negative associate between CD4 count and QoL. The co-morbidity as a negative determinant for QoL among HIV/AIDS infected people. The pooled effect size implies on a relative neutral association, although the confidence interval is wide and ranges between 0.32 to 1.58. The pooled effect size is about 1.82 with confidence interval 1.27 to 2.37 which indicates a considerable positive association with lowest level of heterogeneity. Conclusions The results illustrated that time diagnosing and availability to hospital services had significant relationship with a higher QoL and CD4 < 200 was associated with a lower QoL. In conclusion, policy makers should set an agenda setting to provide a suitable diagnostic and therapeutic facilities to early detecting and continues monitoring the health status of People Who Live with HIV/AIDS (PWLHs’).

scholarly journals Clinical Pharmacology Aspects of Some Tocolytic Drugs Used in Pregnant Women at Risk of Preterm Birth

2019 ◽  
Vol 9 (3) ◽  
pp. 162-166
Author(s):  
E. A. Sоkоvа ◽  
R. A. Chilova ◽  
O. A. Demidova ◽  
K. O. Akopov
Keyword(s):  
Preterm Birth ◽  
Pregnant Women ◽  
Preterm Labour ◽  
Plasma Concentrations ◽  
Cyclooxygenase Inhibitors ◽  
Pharmacokinetic Parameters ◽  
Clinical Effects ◽  
Spontaneous Preterm Birth ◽  
Rational Pharmacotherapy ◽  
The Impact

Spontaneous preterm birth is one of the most pressing issues in obstetrics, as it remains one of the leading causes of newborn morbidity and mortality. Pending issues of aetiology, pathogenesis, and absence of medicinal products indicated for the treatment of spontaneous preterm labour pose a challenge for rational pharmacotherapy. The paper presents the results of a scientific literature review on the problem of rational pharmacotherapy of spontaneous preterm labour using tocolytic drugs — calcium channel blockers, cyclooxygenase inhibitors. The paper summarises specific pharmacokinetic parameters of these drugs during pregnancy. It discusses pharmacogenetic aspects of using tocolytic drugs in pregnant women and their potential clinical effects. It was demonstrated that women with threatened miscarriage had high interindividual variability in nifedipine plasma concentrations depending on CYP3A5 genotype. It was shown that certain genetic polymorphisms of CYP2C9 may lead to an increased metabolic rate and an increase in indomethacin clearance resulting in the reduction of its efficacy. Yet, there is minimal research regarding this issue. Therefore, further research is needed to assess the impact of CYP3A5 and CYP2C9 genotypes on the efficacy and safety of nifedipine and indomethacin used as tocolytic drugs in obstetrics.

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